The Na,K balance of cells is important for many activities including cell volume regulation, protein synthesis, mitochondrial function, cell Ca regulation, excitability and accumulation of organic molecules. Cooling cells of most mammals causes loss of K and gain of Na because of unequal inhibition of active transport and passive permeability. As a conseqence the dependent activities are disrupted and the organism dies, or, in the case of isolated cells, damage occurs. In mammals which hibernate loss of K either does not occur or is less severe; the organism can withstand prolonged periods of profound hypothermia and isolated cells from these species are also better able to survive cold exposure. The continuing aim of this project is to analyze the mechanisms of this cold resistance of membrane function, especially the Na/K transport and conversely to use the peculiar properties of the cells of hibernators as a tool for the analysis of transport mechanisms. Essential to this is the comparison of differences in mechanism among tissues and the changes which occur in a single type of cell with onset of hibernation with cold acclimation of the cell. Our chief objects for these purposes are erythrocytes and kidney cells. Since we use kidney in culture a new objective is to determine how much their properties diverge from those of cells of intact renal tubules.